Process for the purification of mandelic acid N,N-diethylamide

The present invention relates to a process for the purification of mandelic acid N,N-diethylamide, abbreviated DEM herein. This compound ##STR1## and related mandelamides are useful as insect repellents as described in the Swedish Patent 409808 (1979) to W. Thorsell et al.

The synthesis of DEM can be performed by a 4-step route such as described in the above Swedish patent. Whatever the method of synthesis it is important that the crude DEM obtained is upgraded to obtain a purified material suitable for application to the skin.

The purification of DEM is difficult due to:

a) the very high boiling point and the poor thermal stability, which combine to make fractional distillation very difficult on an industrial scale;

b) the low melting point of DEM, 27°-30° C., and the high viscosity, which make it difficult to crystallize DEM.

It is therefore an object of the present invention to provide a process whereby DEM can be purified in a practical way on an industrial scale using ordinary standard equipment.

The essence of the present invention lies in the surprising discovery that DEM forms crystalline, high-melting adducts with calcium halides and water. Preferred halides are selected from chloride and bromide, and embodiments wherein the halide is chloride are particularly preferred.

More specifically, we particularly prefer two different adducts with the compositions DEM·CaCl 2 ·2H 2 O and DEM·CaCl 2 ·6H 2 O, respectively.

Any of such adducts of DEM with calcium halides and water can be used in the purification of DEM by crystallization.

The novel adducts according to the invention are stable in the presence of sufficiently hydrophobic non-polar or moderately polar solvents such as hydrocarbons, ethers and esters. Solvents of these types are therefore useful crystallization media and will serve to dissolve the impurities that are to be removed.

Although the present invention covers any adducts with calcium halides and water the invention will be illustrated in the following mainly with reference to adducts with calcium chloride and water.

The crystallization of DEM as the adduct with 2H 2 O can be performed by stirring the calculated amount of CaCl 2 ·2H 2 O with a solution of DEM in a solvent. The CaCl 2 ·2H 2 O will dissolve due to adduct formation and DEM·CaCl 2 ·2H 2 O will then crystallize rapidly from the solution.

In a modified procedure a hydrophilic solvent such as water or a lower alcohol is added to redissolve the DEM·CaCl 2 ·2H 2 O or to prevent it from precipitating too rapidly. The crystallization may then be completed by distilling off the hydrophilic solvent.

The adduct with 6H 2 O can be crystallized by contacting a solution of DEM in a sufficiently hydrophobic solvent with an approximately 50% aqueous solution of CaCl 2 , corresponding to CaCl 2 ·6H 2 O. When the two essentially immiscible solutions are stirred together, crystals of DEM·CaCl 2 ·6H 2 O will start forming. The process is typically performed at room temperature and the crystallization takes place at a convenient rate if moderate stirring is applied. A high yield of good crystals can thus be obtained in as little as one half hour, although stirring is preferably continued for one or a few hours.

The crystals of DEM·CaCl 2 ·2H 2 O or DEM·CaCl 2 ·6H 2 O thus obtained are typically almost colourless. They are separated from the coloured mother liquor by filtration or centrifugation and washed with solvent. Purified DEM is then set free by stirring the crystals, normally in the presence of adhering solvent, with a suitable amount of water. DEM, together with any solvent, is obtained as an oil phase that separates from the aqueous phase containing the calcium chloride.

After collecting the DEM phase any traces of calcium chloride are removed by extracting with water. Evaporation of solvent leaves DEM of high purity.

The present invention will now be further exemplified by non-limiting examples.